Onset of action

The onset of action is fast (within 60 seconds) for the intravenous anesthetic agents and somewhat slower for inhalation and local anesthetics. The induction time for inhalation agents is a function of the equiUbrium estabUshed between the alveolar concentration relative to the inspired concentration of the gas. Onset of anesthesia can be enhanced by increasing the inspired concentration to approximately twice the desired alveolar concentration, then reducing the concentration once induction is achieved (3). The onset of local anesthetic action is influenced by the site, route, dosage (volume and concentration), and pH at the injection site. 

Propanidid. Propanidid [1421-14-3] (Epontol), C gH2yNO, (7) a derivative of the propyl ester of homo vanillic acid, has been in clinical use in Europe for a number of years. Its main advantage is rapid onset of action and a fast recovery which, like etomidate, is because of rapid metaboHsm by esterases rather than redistribution (108). Excretion is rapid 75 to 90% of the dmg is eliminated as metaboUtes within two hours. Propanidid side effects include hypotension, tachycardia, and hyperventilation followed by apnea, as well as excitatory side effects such as tremor and involuntary muscle movement (109). 

Morphine has certain undesirable side effects. Among these are respiratory depression, nausea, and vomiting, depression of the cough reflex, cardiovascular depression and hypotension, smooth muscle contraction (constipation), and histamine release (93). Morphine s onset of action, duration, and low therapeutic indices have prompted a search for a more effective opiate iv anesthetic. Extreme simplification of the complex morphine molecule has resulted in anilido —piperidines, the fentanyl class of extremely potent opiate iv anesthetics (118,119). 

Neuroleptic analgesia is so called because the combination of a major tranquilizer, a neuroleptic dmg, and a potent opiate produces an anesthetic state characterized by sedation, apathy, and mental detachment (see Psychopharmacological agents) (152). Iimovar [8067-59-2] a combination of droperidol [648-72-2], C22H22FN2O2, (19) and fentanyl (9) citrate, is used for procedures that do not require muscle relaxation. However, the onset of action is slow. 

The second-generation antidepressants, particularly RIMAs and SSRJs, are much less toxic ia overdose than the older TCAs and irreversible MAO inhibitors. However, similar to first-generation antidepressants, the therapeutic effect only becomes manifest after several weeks. Up to one-third of depressed patients are nonresponders. Ideally, an antidepressant would combine a more rapid onset of action with greater clinical efficacy and a higher responder rate, as well as even better tolerability. 

Bopindolol is a long-acting, nonselective P-adrenoceptor blocker. It has mild membrane stabilizing activity and ISA. In vivo, the compound is hydrolyzed to its active metabohte. Because of this prodmg feature the onset of action is slower than other available P-adrenoceptor blockers. Preliminary pharmacokinetic studies indicate that the compound is weU absorbed, is 70% bioavailable, and peak plasma levels are achieved in about 2 h. Whereas its elimination half-life is 4—8 h, P-adrenoceptor blocking action (- 40%) is stiU apparent after 48 h. The dmg is being studied in hypertension, angina, and arrhythmias (43). 

Other Glass III Antiarrhythmic Agents. Clofihum phosphate is a benzene-butanaminium derivative that has highly specific Class III antiarrhythmic activity. It is orahy active, has a rapid onset of action, and a reasonably long duration of antiarrhythmic activity. In preliminary clinical studies, clofihum has shown efficacy against spontaneous ventricular tachycardias (69). 

Po adrninistered nifedipine is almost completely absorbed. The onset of action is 20 min and peak effects occur at 1—2 h. The principal route of elimination is through hepatic metaboHsm by oxidation to hydroxycarboxyHc acid and the corresponding lactone. These metaboHtes are pharmacologically inactive. Almost 70—80% of dmg is eliminated in the urine during the first 24 h. About 15% is excreted in the feces. The elimination half-life of nifedipine is about 1—2.5 h (1,98,99). Frequency of occurrence of side effects in patients is about 17% with about 5% requiring discontinuation of therapy (1,98,99). 

Some of the criteria used in the selection of a suitable agent are effectiveness in extremely small concentrations time to onset of action effectiveness through various routes of entry into the body, such as the respiratory tract, eyes, and skin stability in long-term storage and ease of dissernination in feasible munitions. 

Some alicyclic 1,2-diamine derivatives have recently been shown to have interesting CNS properties. For example, eclanamine (34) is an antidepressant with a rapid onset of action. The reasons for its potency are not as yet clear but pharmacologists note that the drug desensitizes adrenergic alpha-2 receptors and antagonizes the actions of clonidine. The synthesis of eclanamine starts with attack of cyclopentene oxide (30) by dimethylamine (to give 31). This product is converted to the mesylate by reaction with sodium hydride followed by mesyl chloride. Attack of... 

The very slow onset of action and side effects which follow from the anticholinergic side effects characteristic of the tricyclic antidepressants has led to a continuing effort to find replacements from other structural classes which might thus be devoid of this defect. A series of alkoxy phenylpropylamines has been investigated extensively in this search for non-tricyclic antidepressants. The most recent analogue, tomoxetine (69), is accessible by the same route [15] used to prepare the earlier analogue, nisoxetine, in which methoxyl replaces the ortho methyl group. 

These include atropine, scopolamine (hyoscine), trihexyphenidyl (benzhexol) and benzatropine. They block central muscarinic receptors involved in various afferent pathways of the vomiting reflex (Fig. 1). They have been used to control motion sickness, emesis in Meniere s disease and postoperative vomiting. Currently, hyoscine is largely restricted to the treatment of motion sickness where it has a fast onset of action but a short duration (4-6 h). Administration of hyoscine by transdermal patch produces a prolonged, low-level release of the drug with minimal side effects. To control postoperative vomiting, it should be applied >8 h before emesis is anticipated. 

An anesthetic gas, cyclopropane has a rapid onset of action and may be used for induction and maintenance of anesthesia Skeletal muscle relaxation is produced with full anesthetic doses. Cyclopropane is supplied in orange cylinders. Disadvantages of cyclopropane are difficulty in detecting the planes of anesthesia, occasional laryngospasm, cardiac arrhythmias, and postanesthesia nausea, vomiting, and headache Cyclopropane and oxygen mixtures are explosive, which limits the use of this gas anesthetic. 

Ethylene is an anesthetic gas with a rapid onset of action and a rapid recovery from its anesthetic effects. It provides adequate analgesia but has poor muscle-relaxant properties. The advantages of ethylene include minimal bronchospasm, laryngospasm, and postanesthesia vomiting. A disadvantage of ethylene is hypoxia. This gas is supplied in red cylinders. Mixtures of ethylene and oxygen are flammable and explosive. 

An inhaled sympathomimetic, such as albuterol, may be prescribed initially. Salmeterol, a long-acting (5-agonist, is contraindicated because of its slowed onset of action. During an acute bronchospasm, the nurse checks the blood pressure pulse, respiratory rate, and response to the drug every 15 to 35 minutes until the patient s condition stabilizes and respiratory distress is relieved. 

Originally, PCP entered the illegal drug market in the form of tablets, which had a slow onset of action. Since the 1970s, PCP has been produced in... 

In many countries, glucocorticosteroids are administered as first drug because of their well-known antiallergic effects. However, the onset of action of corticosteroids takes at... 

Heparin and warfarin are widely used in the treatment of thrombotic and thromboembolic conditions, such as deep vein thrombosis and pulmonary embolus. Heparin is administered first, because of its prompt onset of action, whereas warfarin takes several days to reach full effect. Their effects are closely monitored by use of appropriate tests of coagulation (see below) because of the risk of producing hemorrhage. 

Keck PE, McElroy SL, Bennett JA (1996a). Health-economic implications of the onset of action of antimanic agents. / Clin Psychiatry 57 (suppl. 13), 13-18. 

The opioid antagonists naloxone and naltrexone bind to aU three opioid receptors, p, K, and 8. These compounds are antagonists due to their inability to elicit downstream effects of these receptors once bound (Sarton et al. 2008 Yaksh and Rudy 1977). Interestingly, both antagonists have a high binding affinity for MORs. Naloxone is used to reverse the effects of an acute opioid overdose because of its rapid onset of action. Naltrexone elicits similar actions, but has a longer onset and duration of action and hence, is used for the maintenance of treatment for opioid addicts. 

Ticlopidine inhibits the P2Yj2 platelet ADP receptor, thus inhibiting ADP-dependent activation of the GP Ilb/IIIa receptor. It has a slow onset of action and takes 3-7 days to reach its maximal antiplatelet effect. It is inactive in vitro and must undergo activation by the hepatic cytochrome p450 enzyme system. Secondary prevention trials have found that ticlopidine-treated patients have an estimated RRR of 33% for the composite endpoint of stroke, myocardial infarction, or vascular death after ischemic stroke. Significant adverse effects include bone marrow depression, rash, diarrhea, and thrombotic thrombocytopenic purpura. No clinical trials have studied ticlopidine for the treatment of stroke in the acute phase. 

Agent Dosing (pg/minute) Onset of Action Side Effects Misc... 

Labetalol 3-6 hour 5-10 minute 10-120 mg/hour Conduction block, heart failure, bradycardia, bronchospasm, exacerbate underlying pulmonary disease Rapid onset of action... 

Currently, hopes for compounds with greater clinical efficacy and faster onset of action than buspirone rest on the development of selective ligands for 5-HT receptors. So far, antagonists of 5-HT2a/c (e-g- ritanserin), 5-HTs (e.g. ondansetron) and 5-HT4 (e.g. zacopride) receptors have all been explored but their anti-anxiety effects are, at best, equivocal. Full appraisals of the role of 5-HT systems in anxiety and the actions of anti-anxiety drugs are to be found in Handley (1995), Barnes and Sharp (1999) and Olivier, van Wijngaarden and Soudijn (2000). 

Amongst the ethers 36 with p-formyl group the 5,6-benzo-substituted compound 36c was found to exhibit maximum activity. The ethers with the ortho formyl group 39a showed a quick onset of action initially, then the... 

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